title: Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks.
abstract: The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.
authors.affiliation: Department of Molecular Biology, Sciences III, University of Geneva, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Saini
authors.forename: André
authors.initials: A
authors.lastname: Liani
authors.forename: Thomas
authors.initials: T
authors.lastname: Curie
authors.forename: Pascal
authors.initials: P
authors.lastname: Gos
authors.forename: Florian
authors.initials: F
authors.lastname: Kreppel
authors.forename: Yann
authors.initials: Y
authors.lastname: Emmenegger
authors.forename: Luigi
authors.initials: L
authors.lastname: Bonacina
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Wolf
authors.forename: Yves-Alain
authors.initials: YA
authors.lastname: Poget
authors.forename: Paul
authors.initials: P
authors.lastname: Franken
authors.forename: Ueli
authors.initials: U
authors.lastname: Schibler
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000601:surgery
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse
keywords: SCN lesion; circadian gene expression; liver oscillators; real-time bioluminescence monitoring; resetting cues